Hofmann, Claudia and Chen, Ning and Obermeier, Florian and Paul, Gisela and Buechler, Christa and Kopp, Andrea and Falk, Werner and Schaeffler, Andreas (2011) C1q/TNF-related Protein-3 (CTRP-3) Is Secreted by Visceral Adipose Tissue and Exerts Antiinflammatory and Antifibrotic Effects in Primary Human Colonic Fibroblasts. INFLAMMATORY BOWEL DISEASES, 17 (12). pp. 2462-2471. ISSN 1078-0998,
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Background: The adipokine CTRP-3 (C1q/TNF-related protein-3) belongs to the C1q/TNF-related protein family which antagonizes the effects of lipopolysaccharide (LPS). The aim was to investigate the antiinflammatory and antifibrotic role of CTRP-3 in Crohn's disease (CD). Methods: Mesenteric adipose tissue (MAT) of patients with CD or colonic cancer (CC) was resected. Human primary colonic lamina propria fibroblasts (CLPF) were isolated from controls and CD patients. Concentrations of chemokines and cytokines in the supernatants were measured by enzyme-linked immunosorbent assay (ELISA). Expression of connective tissue growth factor (CTGF), collagen I, and collagen III was analyzed by real-time polymerase chain reaction (PCR). Recombinant CTRP-3 expressed in insect cells was used for stimulation experiments. Results: CTRP-3 is synthesized and secreted by MAT resected from patients with CD, ulcerative colitis (UC), CC, and sigma diverticulitis as well as by murine and human mature adipocytes. CTRP-3 had no effect on the basal secretion of MCSF, MIF, or RANTES in MAT of CD and control patients. LPS-stimulation (10 ng/mL) significantly increased IL-8 release in CLPF of CD patients and, to a lesser extent, in cells of controls and of fibrotic CD tissue. CTRP-3 significantly and dose-dependently reduced LPS-induced IL-8 secretion in CLPF within 8 hours after LPS exposure, whereas LPS-induced IL-6 and TNF release was not affected. CTRP-3 inhibited TGF-beta production and the expression of CTGF and collagen I in CLPF, whereas collagen III expression remained unchanged. Conclusions: CTRP-3 exerts potent antiinflammatory and antifibrotic effects in CLPF by antagonizing the LPS pathway and by targeting the TGF-beta-CTGF-collagen I pathway. (Inflamm Bowel Dis 2011;17:2462-2471)
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | REPEAT-CONTAINING SEQUENCE; CROHNS-DISEASE; COLLAGENOUS REPEAT; CREEPING FAT; 26-KDA PROTEIN; GROWTH-FACTOR; CHROMOSOMAL LOCALIZATION; PROMOTES PROLIFERATION; GENOMIC ORGANIZATION; CELL-PROLIFERATION; Crohn's disease; adipose tissue; CTRP-3; colonic fibroblasts |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 May 2020 08:59 |
| Last Modified: | 26 May 2020 08:59 |
| URI: | https://pred.uni-regensburg.de/id/eprint/19742 |
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